Programmed cell death, or apoptosis, plays an integral role in cell turnover. Imbalance of apoptosis characterised by a marked increase or decrease of apoptosis relative to cell regeneration, is often associated with disease (Thompson, 1995). For example, excessive apoptosis is characteristic of vascular disorders (Stefanec, 2000), neurodegenerative diseases (Rimon et at. 1997), myelodysplastic syndromes (Parker & Mufti, 2001), ischaemia/reperfusion injury (Gottlieb & Engler, 1999), organ transplant rejection (Krams and Martinez, 1998), tumours and cancers, among others.
However, there are no specific measures of apoptosis used in patient diagnosis or therapy. This is in part due to the lack of a convenient and sensitive marker to monitor apoptosis in vivo. Therefore, a selective marker for apoptotic cells would be advantageous in disease diagnosis and therapy, and would also be of interest for imaging normal cell processes.
Accordingly, there is a need to selectively target active agents to sites of therapeutic or diagnostic interest in particular, there is a need to selectively target agents to apoptotic cells.
The present invention relates to a method of targeting an active agent to apoptotic cells in a vertebrate, comprising administering to a vertebrate a system comprising an arsenoxide (or arsenoxide equivalent) compound and an active agent, wherein the system selectively targets apoptotic cells. The arsenoxide (or arsenoxide equivalent) compound functions primarily as a targeting agent for delivering an active agents such as a therapeutic or imaging agent, to apoptotic cells with a relatively high degree of specificity. A particular advantage of the present invention is that the arsenoxide (or arsenoxide equivalent) compound is selectively taken up by apoptotic cells, and binds to a number of proteins within the cell.